52 articles - From Saturday Feb 19 2022 to Friday Feb 25 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Am J Hematol |
| Blood Adv |
ASH, ABHH, ACHO, Grupo CAHT, Grupo This guideline ADOLOPMENT project highlighted the importance of contextualization of recommendations in other settings, based on differences in values, resources, feasibility, and health equity impact. |
meta-analyses and systematic reviews
| Blood Adv |
Laboratory Assays of VWF Activity and Use of Desmopressin Trials in the Diagnosis of VWD: A Systematic Review and Meta-Analysis. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with VWD suspected of type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Decitabine and Vorinostat with FLAG Chemotherapy in Pediatric Relapsed/Refractory AML: Report from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium. Twelve subjects (34%) had known epigenetic alterations with 8 (67%) achieving a CR, 7 (88%) of whom were MRD negative. Correlative pharmacodynamics demonstrated biologic activity of decitabine and vorinostat and identified specific gene enrichment signatures in non-responding patients. Overall, this therapy was well-tolerated, biologically active, and effective in pediatric patients with R/R AML, particularly those with epigenetic alterations. |
Expression of p53 protein isoforms predicts survival in patients with multiple myeloma. Multivariate Cox models identified high levels of TAp53ß/ |
Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia: Phase 2, multicenter, open-label study. No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, Phase 3 study is nearing completion. |
Safety and efficacy of a humanized CD19 chimeric antigen receptor T Cells for relapsed/refractory acute lymphoblastic leukaemia. ADA positivity was correlated with the disease relapse risk. ADA-positive patients had a significantly lower CAR copy number than ADA-negative patients at the time of recurrence (P < |
| Ann Oncol |
Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIP Michelangelo randomized study. The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis the presence of PD-L1 expression was the most significant factor influencing rate of pCR (OR 2.08). Continuing follow up for the event-free survival is ongoing, and molecular studies are under way. |
| Blood |
Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia. The immunophenotype was characterized by CD10 negativity and IgM positivity. Among 16 patients with known clinical response, 9 (56.3%) had high-risk features including relapse (n = 4) or minimal residual disease >1% at the end of remission induction (n = 5). CDX2-deregulated, UBTF::ATXN7L3 rearranged -B-ALL is a high risk subtype of leukemia in young adults for which novel therapeutic approaches are required. |
Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort. Most common grade =3 adverse events were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free, fixed-duration regimen for patients with CLL. Fixed-duration ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features. |
SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. Using MM patients' primary bone marrow cells, we confirmed that SAR442085 had an increased ability to engage Fc |
| Blood Adv |
An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma. Rituximab maintenance was associated with longer PFS (HR=0.16, 95%CI 0.04-0.71; P=0.016) but did not impact OS. BR is a highly effective upfront regimen in EMZL providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes-zoster and thus prophylactic treatment may be considered. |
Changes in body mass index, weight, and height in children with acute myeloid leukemia and the associations with outcome. Baseline BMI category and Z-score were not associated with outcomes, but higher weight Z-scores were associated with lower incidences of refractory or relapsed disease (HR, 0.82; 95% confidence interval [CI], 0.67-0.99) and higher incidences of death in remission (HR, 1.31; 95% CI, 1.01-1.70). Furthermore, weight Z-score decrease during induction therapy was associated with gastrointestinal, hepatic, and infection toxicities during subsequent therapy and with death in remission (hazard ratio, 2.66; 95% CI, 1.11-6.45). Multidisciplinary monitoring for weight changes and short stature is required from diagnosis to the off-therapy period. |
Clinical Care Pathway for Suspected Vaccine-Induced Immune Thrombotic Thrombocytopenia After ChAdOx1 nCoV-19 vaccination. Three patients had thrombocytopenia and thrombosis with D-dimer levels >4.0 mg/L FEU but had negative PF4-ELISA and SRA results. Patients with VITT were treated successfully with intravenous immunoglobulin, non-heparin anticoagulants and corticosteroids. Our pathway demonstrated that thrombosis is common among patients investigated for VITT and that PF4-ELISA testing is necessary to confirm VITT in those presenting with thrombosis and thrombocytopenia. |
Genome-wide CRISPR/Cas9 screening identifies determinant of panobinostat sensitivity in acute lymphoblastic leukemia. Mechanistically, ectopic SIRT1 expression activated mitochondrial activity and sensitized ALL to panobinostat through activating mitochondria-related apoptosis pathway. Meanwhile, the transcription level of SIRT1 was significantly associated with panobinostat sensitivity across diverse tumor types and thus could be a potential biomarker of panobinostat response in cancers. Our data suggest that patients with higher SIRT1 expression in cancer cells might benefit from panobinostat treatment, supporting the implementation of combinatorial therapy with SIRT1 or mitochondrial activators to overcome panobinostat resistance. |
Lasting shift in the gut microbiota in patients with acute myeloid leukemia. Despite major reductions in antibiotic pressure and other disturbances to the microbiota after hospital discharge, the trajectory of microbiota recovery yields new communities that are highly dissimilar to baseline. This lasting shift in the gut microbiota is relevant for subsequent phases of curative therapy and is a potential target for novel microbiota protective/restorative interventions. This trial is registered at as # NCT03316456. |
Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA. A decrease in the cfDNA VAF was detected in patients responding to therapy, but not in non-responding patients. Of note, cfDNA analysis also showed cytogenetic evolution in 2 cases not responding to treatment. In conclusion, although further studies with larger cohorts are required, our results support the analysis of cfDNA as a promising strategy for performing molecular characterization, detection of chromosomal aberrations and monitoring of MDS patients. |
| Blood Cancer J |
Isolated anemia in patients with large granular lymphocytic leukemia (LGLL). No significant difference in overall survival was noted between PRCA and non-PRCA patients. In summary, this study demonstrates the unique features of LGLL with isolated anemia and underscores the importance of recognizing LGLL as a potential cause of isolated anemia, which may benefit from disease-specific treatment. LGLL patients with PRCA were more likely to require treatment but demonstrated similar clinicopathologic features, therapeutic responses, and overall survival compared to isolated anemia without PRCA, suggesting PRCA and non-PRCA of T-LGLL belong to a common disease spectrum. |
| Haematologica |
Antiplatelet antibody predicts platelet desialylation and apoptosis in immune thrombocytopenia. In ITP patients with anti-GPIIb/IIIa antibodies, both desialylation and apoptosis were dependent on Fc-gamma RIIa signalling rather than platelet activation. Finally, we confirmed in a murine model of ITP that destruction of human platelets induced by anti-GPIIb/IIIa antibodies can be prevented with the NEU1 inhibitor oseltamivir. A collaborative clinical trial is warranted to investigate the utility of oseltamivir in the treatment of ITP. |
Pseudo-mutant P53 is a unique phenotype of DNMT3A-mutated pre-leukemia. Treatment with a short peptide that can shift the dynamic equilibrium favoring the WT conformation of P53, specifically eliminated preL-HSPCs that had dysfunctional canonical P53 pathway activity as reflected by single cell RNA sequencing. Our observations shed light upon a possible targetable P53 dysfunction in human preLHSPCs carrying DNMT3A mutations. This opens new avenues for leukemia prevention. |
| Leukemia |
A predictive scoring system for therapy-failure in persons with chronic myeloid leukemia receiving initial imatinib therapy. Cumulative incidences of imatinib-therapy failure and probabilities of FFS among the 5 risk cohorts (very low-, low-, intermediate-, high- and very high-risk) using the IMTF model were significantly different (all p values < 0.001). The IMTF model also correlated with probabilities of progression-free survival and survival (all p values < 0.001). These data should help physicians optimize TKI-therapy strategy at diagnosis in persons with chronic phase CML. |
Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML. Here we focus on mitochondrial electron transfer proteins ETFA and ETFB. Silencing of ETFA and ETFB led to increased mitochondrial activity, mitochondrial stress, and apoptosis in AML cells, but had little to no effect on normal human CD34 + cells. These studies identify a set of proteins that have not previously been associated with leukemia and may ultimately serve as potential targets for therapeutic manipulation to hinder AML progression and help contribute to our understanding of the disease. |
| Thromb Haemost |
Outcome of cancer-associated venous thromboembolism is more favorable among patients with hematologic malignancies than in those with solid tumors. Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies. |
State-of-the-art-mini review: Dual pathway inhibition to reduce arterial and venous thromboembolism. The totality of available data supports the concept that DPI can reduce major and fatal thromboembolic outcomes, including stroke, myocardial infarction, VTE, and cardiovascular death in key patient cohorts, with acceptable risk of bleeding. Further data are needed to refine which patients derive the best net clinical benefit from such an approach. At the same time, other novel agents such as contact pathway inhibitors that reduce thrombin generation without affecting hemostasis - and thus maximize safety - should be assessed in appropriate populations. |
The lesson learned from the new c.2547-1G>T mutation combined with p.R854Q:when a type 2N mutation reveals a quantitative von Willebrand factor defect. While relatives of type 2N homozygotes usually have normal FVIII levels and FVIII/VWF:Ag ratios, relatives of type 2N/type 1 may have high FVIII/VWF:Ag ratios, but their VWF:FVIIIB and/or VWF:FVIIIB/VWF:Ag ratios are always low. Measuring FVIII and VWF levels may therefore suggest type 2N VWD in patients carrying type 2N mutations alone, but not in type 2N combined with quantitative VWF defects. The VWF:FVIIIB test should consequently always be included when exploring VWF function, whatever VWD patient's phenotype. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
| Blood |
| CA Cancer J Clin |
Genetic testing in prostate cancer management: Considerations informing primary care. This review highlights key aspects of genetic testing in PC, the role of clinicians, with a focus on primary care, the importance of obtaining a comprehensive family history, current germline testing guidelines, and the impact on precision PC care. With emerging evidence and guidelines, clinical pathways are needed to facilitate integrated genetic education, testing, and counseling services in appropriately selected patients. There is also a need for providers to understand the field of genetic counseling and how best to collaborate to enhance multidisciplinary patient care. |
Letters to the editors and authors’ replies
| Am J Hematol |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Leukemia |